Stability of maxillary expansion osteotomy using patient-specific fixation implants without necessitating removable appliances: a retrospective analysis.

OBJECTIVE: This study aimed to evaluate the long-term stability of surgical maxillary expansion using patient-specific fixation implants (PSFIs) without intraoral retention. MATERIALS AND METHODS: Fifteen patients who had undergone segmented Le Fort I osteotomy and PSFIs with available preoperative (t0) early (t1) and 1-year follow-up computed tomography (CT) scans (t2) were evaluated. The early and 1-year 3D models were superimposed to transfer the bony landmarks; the distances between each pair of landmarks at the different time points were then measured. The distances between the canines and second molars were also measured directly on the CT scans. RESULTS: The achieved maxillary expansions ranged from a median of 4.39 (2.00-6.27) mm at the greater palatine foramina to a median of 2.14 (1.56-2 > 83) mm at the canine level of the palatal bone. One year postoperatively, the changes in skeletal diameters ranged from a median of - 0.53 (- 1.65 to 0.41) mm at the greater palatine foramina (p = 0.12) to 0.17 (- 0.09 to 0.32) mm at the canine level of the palatal bone (p = 0.56). Changes in dental arch diameters ranged from a median of - 0.6 (- 2 to 0.00) mm between the second molars to - 1.3 (- 1.8 to - 0.25) mm between the canines (P < 0.05). CONCLUSION: This study showed the stability of maxillary expansion osteotomy using PSFIs, even without postoperative intraoral retention. CLINICAL RELEVANCE: PSFIs are a reliable method for the surgical treatment of transverse maxillary discrepancy. PFSIs are easy-to-use and improve surgical accuracy.

Custom surgical management of invasive malignant tumors of the scalp.

BACKGROUND: There is no universal management protocol concerning invasive malignant tumors of the scalp with bone and dura mater invasion. The aims of this study were to report and discuss our experience in the management of these forms of tumors. METHODS: We retrospectively reviewed all consecutive patients of microsurgical scalp reconstruction performed after resection of invasive cutaneous malignancies of the scalp, calvarium, and dura mater from 2017 to 2019, at Pitié-Salpêtrière University Hospital (Paris, France). RESULTS: Five patients met inclusion criteria. There were three squamous cell carcinomas and two sarcomas. Mean age at surgery was 63.6 years. The sex ratio male/female was 4. Two received radiation prior to resection and two patients had a history of prior scalp tumor surgery. All the patients underwent craniectomy and the mean cranial defect size was 41 cm2. Cranioplasty was performed in one patient. Soft tissue coverage was provided by free tissue transfer of latissimus dorsi muscle in all patients. In four patients, split thickness skin graft was performed in a second surgical stage few weeks later. There were no intraoperative complications and no complications into the donor site for the tissue transfer or the skin graft. Two patients had flap necrosis that healed after a new free flap of latissimus dorsi. CONCLUSIONS: Wide resection with craniectomy and reconstruction with microvascular free tissue transfer provides safe and reliable treatment of recalcitrant invasive scalp skin cancers. The surgical management of these complex patients is a challenge that must be conducted by trained, experienced, and multidisciplinary teams.

Bibliometric analysis of a century of research on oral erythroplakia and leukoplakia.

BACKGROUND: Oral squamous cell carcinoma is a major cause of cancer-associated morbidity and mortality and may develop from oral erythroplakia and leukoplakia (OEL), the most common oral potentially malignant lesions. Our objective was to provide a descriptive overview of the global research activity on OEL over the past decades. METHODS: We performed a systematic bibliometric analysis of articles and reviews on OEL up to December 31st 2016 using the SCOPUS database. Contribution of each country was analyzed by density-equalizing mapping (DEMP). The overall scientific productivity was analyzed for each journal and country. RESULTS: A total of 5098 published items (articles or reviews) were identified. They are expected to double by 2040, with an expected number of 400 items per year. Only 4% of all research on oral oncology is focused on OEL. Together with the increasing number of publications since 1980s, an increasing number of international collaborative studies were observed. Journal of Oral Pathology and Medicine and Oral Oncology are the leading journals in terms of number of published items. The US, India, and the UK were the most prolific countries in terms of publications overtime. CONCLUSIONS: We identified the leading journals as well as the leading authors and countries contributing to the research on OEL. International collaborative studies in the field are to be encouraged to refine strategies of oral cancer prevention.

A 13-gene expression-based radioresistance score highlights the heterogeneity in the response to radiation therapy across HPV-negative HNSCC molecular subtypes.

BACKGROUND: Radiotherapy for head and neck squamous cell carcinomas (HNSCC) is associated with a substantial morbidity and inconsistent efficacy. Human papillomavirus (HPV)-positive status is recognized as a marker of increased radiosensitivity. Our goal was to identify molecular markers associated with benefit to radiotherapy in patients with HPV-negative disease. METHODS: Gene expression profiles from public repositories were downloaded for data mining. Training sets included 421 HPV-negative HNSCC tumors from The Cancer Genome Atlas (TCGA) and 32 HNSCC cell lines with available radiosensitivity data (GSE79368). A radioresistance (RadR) score was computed using the single sample Gene Set Enrichment Analysis tool. The validation sets included two panels of cell lines (NCI-60 and GSE21644) and HPV-negative HNSCC tumor datasets, including 44 (GSE6631), 82 (GSE39366), and 179 (GSE65858) patients, respectively. We finally performed an integrated analysis of the RadR score with known recurrent genomic alterations in HNSCC, patterns of protein expression, biological hallmarks, and patterns of drug sensitivity using TCGA and the E-MTAB-3610 dataset (659 pancancer cell lines, 140 drugs). RESULTS: We identified 13 genes differentially expressed between tumor and normal head and neck mucosa that were associated with radioresistance in vitro and in patients. The 13-gene expression-based RadR score was associated with recurrence in patients treated with surgery and adjuvant radiotherapy but not with surgery alone. It was significantly different among different molecular subtypes of HPV-negative HNSCC and was significantly lower in the "atypical" molecular subtype. An integrated analysis of RadR score with genomic alterations, protein expression, biological hallmarks and patterns of drug sensitivity showed a significant association with CCND1 amplification, fibronectin expression, seven hallmarks (including epithelial-to-mesenchymal transition and unfolded protein response), and increased sensitivity to elesclomol, an HSP90 inhibitor. CONCLUSIONS: Our study highlights the clinical relevance of the molecular classification of HNSCC and the RadR score to refine radiation strategies in HPV-negative disease.

Surface anatomy of the parotid duct and its clinical relevance.

The trajectory of the parotid duct (PD) makes it vulnerable to injuries during facial trauma and facial rejuvenation procedures. The PD is usually represented as a straight line, although its description in the literature varies. Our objective was to study the trajectory of the PD and to define reliable cutaneous landmarks. We dissected 35 human cadaver half-heads. We defined three points: point I where the PD crossed a line (line 2) between point T (the intertragal incisura) and point C (the corner of the mouth), point S for the top of the PD, and point B where the PD penetrated the buccinator muscle. We measured the distance (D) between points T and C, the distance (d1) between points T and I, and the distance (d2) between points T and B. We also determined the height (h) of the orthogonal line between point S and line 2. We noted that for all of the half-heads that we examined, the PD followed a curved trajectory between points I and B above line 2. Point I was located 1/3 of the way along distance D. Point B was tangential to line 2, and was located 2/3 of the way along distance D. The average height measurement (h) was 1.4 cm. We demonstrated that the PD follows a curved trajectory from the 1/3 mark to the 2/3 mark along distance D, the top of this curve being 1.5 cm above the line TC.

Postoperative infections after sinus lifts and onlay grafts in penicillin allergic patients.

INTRODUCTION: The primary objective of this retrospective study was to determine whether patients treated with clindamycin due to a reported allergy to penicillin have an increased risk of postsurgical infections after sinus lifts and onlay grafts. MATERIAL AND METHODS: A retrospective cohort study was performed on patients who underwent bone reconstruction procedures between October 2018 and December 2020. Data from all patients operated at the Pitié Salpêtrière University Hospital for sinus lifts or onlay grafts were collected. All surgical procedures studied were performed under preoperative and postoperative antibiotic prophylaxis with either amoxicillin (+/- clavulanic acid) or clindamycin for patients with reported penicillin allergy. Bone graft-associated infections as well as graft failures were recorded. RESULTS: In this study, 111 patients received bone reconstructions (89 sinus lifts and 148 onlay grafts). In the sinus lifts group, infections occurred in 5 of 89 sites (5.6 %). The infection rate was 28.5 % (7 graft sites) and only 3.9 % (82 graft sites) for clindamycin and for amoxicillin, respectively. In the onlay graft group, infections occurred in 25 of 148 sites (16.8 %). The infection rate was 56 % and only 12 % for clindamycin (18 graft sites) and for amoxicillin, respectively (130 graft sites). Non-Penicillin treated patients had a higher risk of infection with an odd ratio of 7.8 (95 % CI 1.1-54.8, P = 0.04) and 4.8 (95 % CI 1.9-12.3, P = 0.001) compared with patients receiving amoxicillin for onlay grafts and sinus lifts. CONCLUSION: Penicillin allergy and clindamycin use after sinus lift and onlay graft procedures were associated with a higher rate of infection and may be a risk factor for complications related to bone reconstruction surgery.

Uncovering immune checkpoint heterogeneity in oral squamous cell carcinoma using single cell RNA-sequencing data highlights three subgroups of patients with distinct immune phenotypes.

OBJECTIVES: In head and neck squamous cell carcinoma (HNSCC), PD-1/PD-L1 inhibitors remain inefficient in most patients, which points to the need for better characterization of immune checkpoint (ICP) molecule expression. MATERIAL AND METHODS: We evaluated the expression of 22 ICP ligands (ICPL) in 2,176 malignant cells from 10 patients in a public single-cell RNA-sequencing dataset and in two cohorts of HNSCC patients for which gene expression data are available. RESULTS: Based on ICPL expression, malignant cells formed three distinct clusters characterized either by a strong expression of ICPL together with an immune phenotype linked to IFN-γ response (cluster 1) or by a weak ICPL expression and little response to IFN-γ (clusters 2 and 3). Malignant cells from cluster 3 showed a high PD-L1 expression associated with NRF2 signature. The relevance of 3 groups of patients, i.e "high ICPL/high IFN-γ", "low ICPL/low IFN-γ" or "low ICPL/low IFN-γ/high PD-L1" was confirmed in a cohort of 259 OSCC whole tumor samples from TCGA and in the CLB-IHN cohort including patients treated with PD1/PD-L1 inhibitors. The heterogeneous expression of ICPL among patients' malignant cells was associated with immunologically distinct microenvironments, evaluated with the "hot/cold" and the Tumor microenvironment (TME) classification. Finally, the "low ICPL/low IFN-γ/high PD-L1" group 3 displayed a poor prognosis in the TCGA cohort. CONCLUSION: Hence, the global picture of ICPL gene expression in malignant cells from HNSCC patients may contribute to the broader issue of improving immunotherapy strategies though a better stratification of patients and the design of new treatment combinations.

Clues for improvement of research in objective structured clinical examination.

While objective clinical structured examination (OSCE) is a worldwide recognized and effective method to assess clinical skills of undergraduate medical students, the latest Ottawa conference on the assessment of competences raised vigorous debates regarding the future and innovations of OSCE. This study aimed to provide a comprehensive view of the global research activity on OSCE over the past decades and to identify clues for its improvement. We performed a bibliometric and scientometric analysis of OSCE papers published until March 2024. We included a description of the overall scientific productivity, as well as an unsupervised analysis of the main topics and the international scientific collaborations. A total of 3,224 items were identified from the Scopus database. There was a sudden spike in publications, especially related to virtual/remote OSCE, from 2020 to 2024. We identified leading journals and countries in terms of number of publications and citations. A co-occurrence term network identified three main clusters corresponding to different topics of research in OSCE. Two connected clusters related to OSCE performance and reliability, and a third cluster on student's experience, mental health (anxiety), and perception with few connections to the two previous clusters. Finally, the United States, the United Kingdom, and Canada were identified as leading countries in terms of scientific publications and collaborations in an international scientific network involving other European countries (the Netherlands, Belgium, Italy) as well as Saudi Arabia and Australia, and revealed the lack of important collaboration with Asian countries. Various avenues for improving OSCE research have been identified: i) developing remote OSCE with comparative studies between live and remote OSCE and issuing international recommendations for sharing remote OSCE between universities and countries; ii) fostering international collaborative studies with the support of key collaborating countries; iii) investigating the relationships between student performance and anxiety.

Reliability of gene-expression profiling from tumor biopsy for refining neoadjuvant strategies in patients with head and neck squamous cell carcinoma.

While recent clinical trials evaluating neoadjuvant immune checkpoint inhibitors showed promising results in a subset of patients with head and neck squamous cell carcinomas (HNSCC), there is a need for the identification of robust biomarkers in tumor biopsies to improve patient selection. This context suggests unravelling transcriptomic heterogeneity between untreated paired samples from same patient with HNSCC. Based on previous studies and the analysis of publicly available gene expression profiles of paired tumor biopsies and surgical resection specimens, we discuss the reliability of tumor biopsy to capture the overall activation of targetable biological pathways in patients with HNSCC. Further studies investigating intratumor transcriptomic heterogeneity as well as the effect of sampling methods on gene expression are needed in patients with HNSCC, in order to develop innovative and relevant biomarker-driven neoadjuvant strategies.

Biomarkers of radioresistance in head and neck squamous cell carcinomas.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality. Although HNSCC is mainly caused by tobacco and alcohol consumption, infection by Human Papilloma Virus (HPV) has been also associated with the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCC) during the past decades. HPV-positive HNSCC is characterized by a higher radiosensitivity compared to HPV-negative tumor. While several clinical trials are evaluating de-escaladed radiation doses strategies in HPV-positive HNSCC, molecular mechanisms associated with relative radioresistance in HPV-negative HNSCC are still broadly unknown. Our goal was to review recently proposed biomarkers of radioresistance in this setting, which may be useful for stratifying tumor's patient according to predicted level of radioresistance. CONCLUSIONS: most of biomarkers of radioresistance in HPV-negative HNSCC are identified using a hypothesis-driven approach, based on molecular mechanisms known to play a key role during carcinogenesis, compared to an unsupervised data-driven approach regardless the biological rational. DNA repair and hypoxia are the two most widely investigated biological and targetable pathways related to radioresistance in HNSCC. The better understanding of molecular mechanisms and biomarkers of radioresistance in HPV-negative HNSCC could help for the development of radiosensitization strategies, based on targetable biomarkers, in radioresistant tumors as well as de-escalation radiation dose strategies, based on biological level of radioresistance, in radiosensitive tumors.

Extensive head and neck skin cancers: Carcinologic surgery as a cornerstone of treatment.

BACKGROUND AND OBJECTIVE: The prevalence of extensive skin cancers increases with the aging of the population. Surgical management is the gold standard of curative treatment while morbidity is not negligible. There are few data in the literature concerning extensive head and neck cutaneous cancers. The aim of this article is to report our experience of curative management of head and neck extensive skin cancers. METHOD: In this single-center retrospective observational study, we report a series of 17 patients with extensive skin facial cancers treated by surgery between 2013 and 2022 in the maxillofacial surgery department of the Pitié-Salpêtrière Hospital. We collected clinical, therapeutic, histological, and carcinologic data. RESULTS: The median age of the patients was 66 years [35-94]. There were 9 male and 8 women. Scalp (39 %) and cheek (22 %) locations were the most frequent ones. The most frequent histological types were squamous cell carcinoma (61 %) and basal cell carcinoma (17 %). Three patients received neoadjuvant treatment. The surgical treatment consisted mainly of carcinological resection followed by one-stage reconstruction by free flap for 5 (30 %) patients and without reconstruction for primary for 12 (70 %) patients, of whom 8 benefited from secondary reconstruction. Five patients received adjuvant radiotherapy or radio-chemotherapy. With a median follow-up of 40 months (2-72), the median overall survival was 40 months (12-72). CONCLUSION: We know that extensive skin cancers of the face have a good prognosis on condition that the carcinological and reconstructive requirements are respected. Surgery remains the cornerstone of treatment while the improvement of adjuvant therapies, in particular the rise of immunotherapies or other targeted therapies, may allow to limit recurrences.

Intestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming.

Reactive oxygen species (ROS) are considered to be the main drivers of inflammatory bowel disease. We investigated whether this permanent insult compels intestinal stem cells to develop strategies to dampen the deleterious effects of ROS. As an adverse effect, this adaptation process may increase their tolerance to oncogenic insults and facilitate their neoplastic transformation. We submitted immortalized human colonic epithelial cells to either a mimic of chronic inflammation or to a chemical peroxide, analyzed how they adapted to stress, and addressed the biological relevance of these observations in databases. We demonstrated that cells adapt to chronic-inflammation-associated oxidative stress in vitro through a partial genetic reprogramming. Through a gene set enrichment analysis, we showed that this program is recurrently active in the intestinal mucosae of Crohn's and ulcerative colitis disease patients and evolves alongside disease progression. Based on a previously reported characterization of intestinal stem and precursor cells using tracing experiments, we lastly confirmed the activation of the program in intestinal precursor cells during murine colorectal cancer development. This adaptive process is thus likely to play a role in the progression of Crohn's and ulcerative disease, and potentially in the initiation of colorectal cancer.

Radiomics combined with transcriptomics to predict response to immunotherapy from patients treated with PD-1/PD-L1 inhibitors for advanced NSCLC.

Introduction: In this study, we aim to build radiomics and multiomics models based on transcriptomics and radiomics to predict the response from patients treated with the PD-L1 inhibitor. Materials and methods: One hundred and ninety-five patients treated with PD-1/PD-L1 inhibitors were included. For all patients, 342 radiomic features were extracted from pretreatment computed tomography scans. The training set was built with 110 patients treated at the Léon Bérard Cancer Center. An independent validation cohort was built with the 85 patients treated in Dijon. The two sets were dichotomized into two classes, patients with disease control and those considered non-responders, in order to predict the disease control at 3 months. Various models were trained with different feature selection methods, and different classifiers were evaluated to build the models. In a second exploratory step, we used transcriptomics to enrich the database and develop a multiomic signature of response to immunotherapy in a 54-patient subgroup. Finally, we considered the HOT/COLD status. We first trained a radiomic model to predict the HOT/COLD status and then prototyped a hybrid model integrating radiomics and the HOT/COLD status to predict the response to immunotherapy. Results: Radiomic signature for 3 months' progression-free survival (PFS) classification: The most predictive model had an area under the receiver operating characteristic curve (AUROC) of 0.94 on the training set and 0.65 on the external validation set. This model was obtained with the t-test selection method and with a support vector machine (SVM) classifier. Multiomic signature for PFS classification: The most predictive model had an AUROC of 0.95 on the training set and 0.99 on the validation set. Radiomic model to predict the HOT/COLD status: the most predictive model had an AUROC of 0.93 on the training set and 0.86 on the validation set. HOT/COLD radiomic hybrid model for PFS classification: the most predictive model had an AUROC of 0.93 on the training set and 0.90 on the validation set. Conclusion: In conclusion, radiomics could be used to predict the response to immunotherapy in non-small-cell lung cancer patients. The use of transcriptomics or the HOT/COLD status, together with radiomics, may improve the working of the prediction models.

A Radiomics Approach to Identify Immunologically Active Tumor in Patients with Head and Neck Squamous Cell Carcinomas.

BACKGROUND: We recently developed a gene-expression-based HOT score to identify the hot/cold phenotype of head and neck squamous cell carcinomas (HNSCCs), which is associated with the response to immunotherapy. Our goal was to determine whether radiomic profiling from computed tomography (CT) scans can distinguish hot and cold HNSCC. METHOD: We included 113 patients from The Cancer Genome Atlas (TCGA) and 20 patients from the Groupe Hospitalier Pitié-Salpêtrière (GHPS) with HNSCC, all with available pre-treatment CT scans. The hot/cold phenotype was computed for all patients using the HOT score. The IBEX software (version 4.11.9, accessed on 30 march 2020) was used to extract radiomic features from the delineated tumor region in both datasets, and the intraclass correlation coefficient (ICC) was computed to select robust features. Machine learning classifier models were trained and tested in the TCGA dataset and validated using the area under the receiver operator characteristic curve (AUC) in the GHPS cohort. RESULTS: A total of 144 radiomic features with an ICC >0.9 was selected. An XGBoost model including these selected features showed the best performance prediction of the hot/cold phenotype with AUC = 0.86 in the GHPS validation dataset. CONCLUSIONS AND RELEVANCE: We identified a relevant radiomic model to capture the overall hot/cold phenotype of HNSCC. This non-invasive approach could help with the identification of patients with HNSCC who may benefit from immunotherapy.

An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers.

An accurate estimate of patient survival at diagnosis is critical to plan efficient therapeutic options. A simple and multiapplication tool is needed to move forward the precision medicine era. Taking advantage of the broad and high CD10 expression in stem and cancers cells, we evaluated the molecular identity of aggressive cancer cells. We used epithelial primary cells and developed a breast cancer stem cell­based progressive model. The superiority of the early-transformed isolated molecular index was evaluated by large-scale analysis in solid cancers. BMP2-driven cell transformation increases CD10 expression which preserves stemness properties. Our model identified a unique set of 159 genes enriched in G2­M cell-cycle phases and spindle assembly complex. Using samples predisposed to transformation, we confirmed the value of an early neoplasia index associated to CD10 (ENI10) to discriminate premalignant status of a human tissue. Using a stratified Cox model, a large-scale analysis (>10,000 samples, The Cancer Genome Atlas Pan-Cancer) validated a strong risk gradient (HRs reaching HR = 5.15; 95% confidence interval: 4.00­6.64) for high ENI10 levels. Through different databases, Cox regression model analyses highlighted an association between ENI10 and poor progression-free intervals for more than 50% of cancer subtypes tested, and the potential of ENI10 to predict drug efficacy. The ENI10 index constitutes a robust tool to detect pretransformed tissues and identify high-risk patients at diagnosis. Owing to its biological link with refractory cancer stem cells, the ENI10 index constitutes a unique way of identifying effective treatments to improve clinical care. SIGNIFICANCE: We identified a molecular signature called ENI10 which, owing to its biological link with stem cell properties, predicts patient outcome and drugs efficiency in breast and several other cancers. ENI10 should allow early and optimized clinical management of a broad number of cancers, regardless of the stage of tumor progression.

Maxillofacial free flap surgery outcomes in critical care: a single-center investigation looking for clues to improvement.

BACKGROUND: Maxillofacial surgery for free flap reconstructions is associated with many complications due to technical complexity and comorbidity of patients. With a focus on critical care, the authors studied the impact of complications to highlight predictors of poor postoperative outcomes in order to implement optimization protocols. METHODS: This case-control study analyzed the relationship between perioperative variables and postoperative medical and surgical complications of patients who underwent head and neck surgery using fibular and forearm free flaps. The primary objective was the incidence of prolonged intensive care unit (ICU) length of stay (LOS). Secondary objectives were the incidence of ICU readmissions, postoperative infections, and 1-year mortality. A univariable logistic regression model was used. A study of mortality was performed with survival analysis. Regarding our primary objective, we performed a Benjamini-Hochberg procedure and a multivariable Poisson regression with defined variables of interest. RESULTS: The data of 118 hospital stays were included. Prolonged ICU LOS was observed in 47% of cases and was associated with chronic obstructive pulmonary disease, pneumopathies, intraoperative blood transfusion, and surgical duration. Medical and surgical complications were associated with prolonged ICU LOS. After the Benjamini-Hochberg procedure, infectious complications, complications, major complications, total number of pneumopathies, and operative time remained significant. At least one complication was experienced by 71% of patients during the hospitalization, and 33% of patients suffered from major complications. Infectious complications were the most common (40% of patients) and were mainly caused by pneumonia (25% of patients); these complications were associated with low preoperative hemoglobin level, intraoperative blood transfusion, accumulation of reversible cardiovascular risk factors, chronic alcohol consumption, and duration of surgery. Pneumonia was specifically associated with chronic obstructive pulmonary disease. The ICU readmission rate was 10% and was associated with lower preoperative hemoglobin level, pneumopathies, surgical duration, and use of a fibular flap. The 1-year mortality was 12%, and the survival analysis showed no association with prolonged ICU LOS. Poisson regression showed that ICU LOS was prolonged by smoking history, lower preoperative hemoglobin level, intraoperative blood transfusion, major complication, and pneumopathies. CONCLUSIONS: Practices such as blood management and respiratory prehabilitation could be beneficial and should be evaluated as a part of global improvement strategies.

Identification of a Gene-Expression-Based Surrogate of Genomic Instability during Oral Carcinogenesis.

BACKGROUND: Our goal was to identify a gene-expression-based surrogate of genomic instability (GI) associated with the transformation of oral potentially malignant disorder (OPMD) into oral squamous cell carcinoma (OSCC). METHODS: GI was defined as the fraction of genome altered (FGA). Training sets included the CCLE and TCGA databases. The relevance of the enrichment score of the top correlated genes, referred to as the GIN score, was evaluated in eight independent public datasets from the GEO repository, including a cohort of patients with OPMD with available outcome. RESULTS: A set of 20 genes correlated with FGA in head and neck SCC were identified. A significant correlation was found between the 20-gene based GIN score and FGA in 95 esophagus SCC (r = 0.59) and 501 lung SCC (r = 0.63), and in 33 OPMD/OSCC (r = 0.38). A significantly increased GIN score was observed at different stages of oral carcinogenesis (normal-dysplasia -OSCC) in five independent datasets. The GIN score was higher in 10 OPMD that transformed into oral cancer compared to 10 nontransforming OPMD (p = 0.0288), and was associated with oral-cancer-free survival in 86 patients with OPMD (p = 0.0081). CONCLUSIONS: The GIN score is a gene-expression surrogate of GI, and is associated with oral carcinogenesis and OPMD malignant transformation.

Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.

INTRODUCTION: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. METHODS: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. RESULTS: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. CONCLUSION: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.

Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1/PD-L1 inhibitors.

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.